Approximately 1% of the U.S. population has a urinary stone annually. Some 15-20% of these stones are caused by infection. "Infection stones" commonly manifest clinically as staghorn renal calculi. Conventional medical therapy has had little success in the long-term management of such stones. Surgical therapy can be curative, but stone recurrence is relatively frequent. Recurrent "infection stones" cause more kidneys to be removed than all other forms of stone disease. A chemotherapeutic adjunct to surgical therapy is needed. Experimental studies have shown that struvite (MgNH4PO4) urinary stones caused by infection form primarily as a consequence of the bacterial enzyme urease. Acetohydroxamic acid (AHA) is an effective inhibitor of bacterial urease; its pharmacologic characteristics are favorable for human use. We have shown that AHA maintains urine in an undersaturated state in the presence of urease-producing bacteria. In these studies stone growth was prevented and preformed struvite and apatite crystals dissolved. In preliminary clinical trials AHA has been administered to patients who have chronic urinary tract infection associated with stones. Urinary ammonia, alkalinity and supersaturation with respect to struvite have been reduced. No toxicity has been observed. This application requests funds to complete clinical toxicity studies and to conduct preliminary clinical trials of AHA in patients with recurrent "infection stones." A companion pharmacology proposal entitled "Acetohydroxamic Acid Pharmacokinetics in Rats and Man" will investigate the absorption, distribution and metabolism of AHA. A copy of this proposal is appended.